NHGRI Pays Tribute to a Giant of Medical Genetics

Renowned Father of Medical Genetics, Victor Almon McKusick, 1921-2008

Rarely can one person be credited with establishing an entire branch of medicine, but such is the case for Victor McKusick, M.D., and the field of medical genetics. The much-admired researcher, who almost single-handedly placed genetics into the mainstream of clinical medicine and helped to pioneer the Human Genome Project, died July 22 at his home near Baltimore at the age of 86.

"Victor McKusick is widely and accurately known as the 'Father of Medical Genetics.' His tireless and creative contributions over more than half a century have provided a permanent foundation for a field that now occupies the center of modern medicine," said National Human Genome Research Institute (NHGRI) Director Francis S. Collins, M.D., Ph.D.

NHGRI's Deputy Director, Alan E. Guttmacher, M.D., also fondly remembers the sweeping influence of Dr. McKusick, who was University Professor of Medical Genetics at the Johns Hopkins School of Medicine. "His wisdom and dedication to advancing knowledge and health were remarkable, as was his perpetual willingness to help whenever a colleague had a challenging clinical question. He served as a mentor not only for his numerous trainees at Johns Hopkins, but also for virtually all of us who chose to follow in his footsteps in medical genetics. He will be missed as a scientist, a physician, a role model and a kind man."

Dr. McKusick earned his M.D. from the Johns Hopkins University School of Medicine in 1946 and joined the faculty of the School of Medicine as a cardiologist the same year, studying heart sounds and murmurs. He held joint professorships in epidemiology in the Johns Hopkins University School of Public Health and in biology at the Johns Hopkins University.

He quickly developed an interest in the inheritance of disease, studying patients afflicted with Marfan syndrome, a connective tissue disease marked by unusually tall height, heart defects and other abnormalities. The experience prompted Dr. McKusick to begin cataloging and mapping genes on chromosomes, relating their location to human diseases.

In 1957, he founded the Division of Medical Genetics, which he headed until 1973, when he became the William Osler Professor and chairman of the Department of Medicine, and physician in chief of the Johns Hopkins Hospital. He held these posts until 1985, when he was named University Professor of Medical Genetics.

During the 1960s, McKusick conducted studies of inherited disorders in the Amish that discovered previously unrecognized, inherited conditions, and served as a model for studies in similarly isolated populations. In 1966, he published the first edition of his master compendium of disorders and genetic factors in disease, formally titled Mendelian Inheritance in Man: Catalogs of Autosomal Recessive, and X-Linked Phenotypes. Now known as Online Mendelian Inheritance in Man (OMIM), this landmark resource is continually updated at www.ncbi.nlm.nih.gov/omim and is considered an essential reference for medical geneticists around the globe.

In 1997, when Dr. McKusick was the recipient of the Albert Lasker Award for Lifetime Achievement in Medical Science, Dr. Collins had a conversation with the genetics pioneer about how important Mendelian Inheritance in Man had been to him as a first-year medical genetics fellow at Yale University in 1981. Dr. Collins was confronted with the puzzling case of a young infant where imaging studies suggested a sort of jejunal atresia, a type of intestinal obstruction. Sure enough, there was a family history of an identical lesion in a sibling.

Dr. Collins described the case to his attending physician, Dr. Uta Francke and both were quite puzzled until they looked at Dr. McKusick's book where they found the entry "*243600, Familial Apple Peel Jejunal Atresia."

"There it was, an absolute perfect description of the condition that we had just seen," remembered Dr. Collins. "Whereupon, Uta said,'This is wonderful. Victor should win the Nobel Prize!' "

While editing Mendelian Inheritance in Man was a passion for Dr. McKusick, it was just one of his many ideas that revolutionized the field of medical genetics. In 1969, he proposed mapping all human genes — an idea nearly two decades ahead of its time. In fact, he was an early proponent and skillful architect of the Human Genome Project, which in 2003 successfully completed its effort to sequence all 3.1 billion DNA letters in the human genetic blueprint. Today, the importance of recognizing and understanding the links between various genes and disease proves the merit and the widespread acceptance of Dr. McKusick's fundamental approach to studying disease.

During a career that spanned an impressive 60 years, Dr. McKusick received many accolades in addition to the Lasker Award. These honors included the John Phillips Award of the American College of Physicians for distinguished contributions in internal medicine (1972); the Gairdner International Award (1977); the William A. Allan Award of the American Society of Human Genetics (1977); the James Murray Luck Award from the National Academy of Sciences (1982); the Sanremo International Prize for Genetic Research (1983); the American Association of Physicians' George M. Kober Medal (1990); the National Medal of Science (2001); and the Japan Prize in Medical Genetics and Genomics (2008). McKusick is also a member of the National Academy of Sciences.

"Many of us would not be where we are today without him," Dr. Collins said. "As a geneticist, internist, cardiologist, teacher, mentor, role model, editor and academic leader, he was a giant of our time. We will miss him greatly."